Project Summary This new study, Diagnostic Innovations in Glaucoma Study (DIGS): High Myopia and Advanced Disease, will overcome barriers to detection of progressive OAG in two cohorts of patients who are among the most challenging clinically to manage, OAG patients with advanced disease (advOAG) and OAG patients with high myopia (mypOAG). Determining whether a patient is stable or progressing is particularly difficult for these patients as the structural and functional tests that usually guide treatment decisions are of diminished value. We will also expand our longitudinal reference database of healthy eyes to include older healthy high myopic eyes and use it to improve detection of mypOAG at one point in time and to differentiate between age-related changes and mypOAG progression over time. In addition, we will add Optical Coherence Tomography (OCT) Angiography testing to characterize glaucomatous retinal vascular damage and change and to evaluate its potential role in OAG management in these challenging patients. In Specific Aim 1 (Advanced OAG), we address several hypotheses designed to determine how best to monitor advanced OAG using both standard and novel structural measures. We hypothesize that standard spectral domain OCT ganglion cell measures and central visual field testing may be more effective for monitoring these challenging cases and that novel analysis strategies such as whole 3D volume and new OCT Angiography retinal vascular measures may improve detection of progressive advOAG. In Specific Aim 2 (High Myopia), we address several hypotheses designed to improve our understanding and detection of OAG damage in myopic eyes and to differentiate between age-related change and mypOAG progression using standard and novel structural measures. We hypothesize that establishment of a reference database of healthy myopes, and the incorporation of unique features of the myopic eye will improve detection of OAG and its progression in individuals with high myopia. This proposal will improve our understanding and ability to manage the disease and prevent OAG-related functional impairment and blindness in the most challenging patients. These results can then be used to develop personalized medicine tools to improve the efficiency and reduce the costs of OAG management along the full continuum of OAG severity and range of refractive status.